NF-kappaB activation is required for cisplatin-induced apoptosis in head and neck squamous carcinoma cells.

Abstract

This study demonstrates a requirement for NF-kappaB activation in cis-diamminedichloroplatinum (cisplatin)-induced apoptosis in human head and neck squamous cell carcinoma (HNSCC) cell lines. This conclusion was supported by the following observations: cisplatin induced IkappaBalpha degradation and NF-kappaB-dependent transcriptional activation prior to cell death; pyrrolidine dithiocarbamate (PDTC), a chemical inhibitor of NF-kappaB activation, prevented apoptosis; lactacystin, an inhibitor of IkappaBalpha degradation, also prevented apoptosis; and finally, the expression of a super-repressor mutant IkappaBalpha blocked apoptosis. The expression of tumor necrosis factor alpha (TNFalpha) was promoted by cisplatin treatment and was suppressed by PDTC treatment. In addition, a neutralizing antibody against TNFalpha protected cells from cisplatin-induced apoptosis. These findings suggest that NF-kappaB activation is required for cisplatin-induced apoptosis and TNFalpha may play an important role in NF-kappaB-mediated apoptosis in cisplatin-treated HNSCC cell lines.

• Authors: Seong Bum Kim, Jong Soo Kim, Ji Hye Lee, Won Joon Yoon, Dong Seuk Lee, Myoung Seok Ko, Byung Suk Kwon, Dae Hwa Choi, Hong Rae Cho, Byung Ju Lee, Dae Kyun Chung, Hyeon Woo Lee, Jeong Woo Park
• Journal: FEBS letters (FEBS Lett) Vol. 580 Issue 1 Pg. 311-8 (Jan 09 2006) ISSN: 0014-5793 [Print] England
• PMID: 16376337 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents
• Cysteine Proteinase Inhibitors
• I-kappa B Proteins
• NF-kappa B
• NFKBIA protein, human
• Thiocarbamates
• Tumor Necrosis Factor-alpha
• lactacystin
• NF-KappaB Inhibitor alpha
• Cisplatin
• Acetylcysteine

Topics

• Acetylcysteine (analogs & derivatives, pharmacology)
• Antibodies, Monoclonal (immunology, pharmacology)
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Autocrine Communication (drug effects)
• Carcinoma, Squamous Cell (metabolism)
• Cell Line, Tumor
• Cisplatin (pharmacology)
• Cysteine Proteinase Inhibitors (pharmacology)
• Head and Neck Neoplasms (metabolism)
• Humans
• I-kappa B Proteins (antagonists & inhibitors, metabolism)
• NF-KappaB Inhibitor alpha
• NF-kappa B (antagonists & inhibitors, metabolism)
• Signal Transduction (drug effects)
• Thiocarbamates (pharmacology)
• Tumor Necrosis Factor-alpha (biosynthesis, immunology)